scholarly journals Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 167 ◽  
Author(s):  
Muhammad Nawaz ◽  
Neelam Shah ◽  
Bruna Zanetti ◽  
Marco Maugeri ◽  
Renata Silvestre ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Metabolic Diseases ◽  
Bioactive Molecules ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Pathological Conditions ◽  
Potential Applications ◽  
Non Coding Rnas

Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.

scholarly journals Scar Formation: Cellular Mechanisms

2020 ◽  
pp. 19-26
Author(s):  
Ian A. Darby ◽  
Alexis Desmoulière
Keyword(s):  
Extracellular Matrix ◽  
Tissue Repair ◽  
New Drugs ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Hypertrophic Scars ◽  
Cellular Mechanisms ◽  
Skin Repair ◽  
Cell Quiescence ◽  
Key Players

AbstractFibroblasts are key players in the maintenance of skin homeostasis and in orchestrating physiological tissue repair. Fibroblasts secrete and are embedded in a sophisticated extracellular matrix, and a complex and interactive dialogue exists between fibroblasts and their microenvironment. In addition to the secretion of the extracellular matrix, fibroblasts and myofibroblasts secrete extracellular matrix remodeling enzymes, matrix metalloproteinases and their inhibitors, and tissue inhibitors of metalloproteinases and are thus able to remodel the extracellular matrix. Myofibroblasts and their microenvironment form a network that evolves during tissue repair. This network has reciprocal actions affecting cell differentiation, cell proliferation, cell quiescence, or apoptosis and has actions on growth factor bioavailability by binding, sequestration, and activation. Mechanical forces also play a role in regulating the myofibroblast phenotype as cells are subjected to mechanical stress and mechanical signaling is activated. Innervation is also involved in both skin repair processes and differentiation of myofibroblasts. In pathological situations, for example, in excessive scarring, the dialogue between myofibroblasts and their microenvironment can be altered or disrupted, leading to defects in tissue repair or to pathological scarring, such as that seen in hypertrophic scars. Better understanding of the intimate dialogue between myofibroblasts and their local microenvironment is needed and will be important in aiding the identification of new therapeutic targets and discovery of new drugs to treat or prevent aberrant tissue repair and scarring.

scholarly journals Implications of Skeletal Muscle Extracellular Matrix Remodeling in Metabolic Disorders: Diabetes Perspective

2020 ◽  
Vol 21 (11) ◽  
pp. 3845 ◽  
Author(s):  
Khurshid Ahmad ◽  
Inho Choi ◽  
Yong-Ho Lee
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Matrix Remodeling ◽  
Therapeutic Approaches ◽  
Ecm Remodeling ◽  
Metabolic Dysregulation ◽  
Pathological Conditions ◽  
Insulin Activity

The extracellular matrix (ECM) provides a scaffold for cells, controlling biological processes and providing structural as well as mechanical support to surrounding cells. Disruption of ECM homeostasis results in several pathological conditions. Skeletal muscle ECM is a complex network comprising collagens, proteoglycans, glycoproteins, and elastin. Recent therapeutic approaches targeting ECM remodeling have been extensively deliberated. Various ECM components are typically found to be augmented in the skeletal muscle of obese and/or diabetic humans. Skeletal muscle ECM remodeling is thought to be a feature of the pathogenic milieu allied with metabolic dysregulation, obesity, and eventual diabetes. This narrative review explores the current understanding of key components of skeletal muscle ECM and their specific roles in the regulation of metabolic diseases. Additionally, we discuss muscle-specific integrins and their role in the regulation of insulin sensitivity. A better understanding of the importance of skeletal muscle ECM remodeling, integrin signaling, and other factors that regulate insulin activity may help in the development of novel therapeutics for managing diabetes and other metabolic disorders.

scholarly journals Role of Matrix Metalloproteinases in Angiogenesis and Its Implications in Asthma

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Khuloud Bajbouj ◽  
Rakhee K. Ramakrishnan ◽  
Qutayba Hamid
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Vascular Remodeling ◽  
Proteolytic Enzymes ◽  
Airway Remodeling ◽  
Inflammatory Cells ◽  
Bioactive Molecules ◽  
Matrix Remodeling ◽  
Pathological Conditions

Asthma is a chronic airway disorder associated with aberrant inflammatory and remodeling responses. Angiogenesis and associated vascular remodeling are one of the pathological hallmarks of asthma. The mechanisms underlying angiogenesis in asthmatic airways and its clinical relevance represent a relatively nascent field in asthma when compared to other airway remodeling features. Matrix metalloproteinases (MMPs) are proteases that play an important role in both physiological and pathological conditions. In addition to facilitating extracellular matrix turnover, these proteolytic enzymes cleave bioactive molecules, thereby regulating cell signaling. MMPs have been implicated in the pathogenesis of asthma by interacting with both the airway inflammatory cells and the resident structural cells. MMPs also cover a broad range of angiogenic functions, from the degradation of the vascular basement membrane and extracellular matrix remodeling to the release of a variety of angiogenic mediators and growth factors. This review focuses on the contribution of MMPs and the regulatory role exerted by them in angiogenesis and vascular remodeling in asthma as well as addresses their potential as therapeutic targets in ameliorating angiogenesis in asthma.

scholarly journals Extracellular Vesicles as Biological Shuttles for Targeted Therapies

2019 ◽  
Vol 20 (8) ◽  
pp. 1848 ◽  
Author(s):  
Stefania Raimondo ◽  
Gianluca Giavaresi ◽  
Aurelio Lorico ◽  
Riccardo Alessandro
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Target Cells ◽  
Special Focus ◽  
Pathological Conditions ◽  
Critical Issues ◽  
Membrane Bound ◽  
And Function ◽  
Potential Use

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)—specialized membrane-bound nanocarriers for intercellular communication—suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.

scholarly journals Extracellular Vesicles in Cancer Metabolism: Implications for Cancer Diagnosis and Treatment

2021 ◽  
Vol 20 ◽  
pp. 153303382110378
Author(s):  
Qian Zhang ◽  
Xiangling Yang ◽  
Huanliang Liu
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Diagnosis ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Bioactive Molecules ◽  
Diagnosis And Treatment ◽  
Existing Problems ◽  
Non Coding Rnas

Metabolic reprogramming is one of the most common characteristics of cancer cells. The metabolic alterations of glucose, amino acids and lipids can support the aggressive phenotype of cancer cells. Exosomes, a kind of extracellular vesicles, participate in the intercellular communication through transferring bioactive molecules. Increasing evidence has demonstrated that enzymes, metabolites and non-coding RNAs in exosomes are responsible for the metabolic alteration of cancer cells. In this review, we summarize the past and recent findings of exosomes in altering cancer metabolism and elaborate on the role of the specific enzymes, metabolites and non-coding RNAs transferred by exosomes. Moreover, we give evidence of the role of exosomes in cancer diagnosis and treatment. Finally, we discuss the existing problems in the study and application of exosomes in cancer diagnosis and treatment.

Abstract P016: GYY4137, a Hydrogen Sulfide Donor, Mitigates Ang II-induced Extracellular Matrix Remodeling in Glomerular Endothelial and Mesangial Cells

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Matthew Amin ◽  
Sathnur Pushpakumar ◽  
Sourav Kundu ◽  
Geetansh Tyagi ◽  
Aaron Tyagi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Hydrogen Sulfide ◽  
Mesangial Cells ◽  
Collagen Iv ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Ang Ii ◽  
Hypertensive Nephropathy ◽  
Glomerular Endothelial Cells

Hypertensive nephropathy is associated with progressive alteration of extracellular matrix (ECM) components. Both mesangial and glomerular endothelial cells have the ability to synthesize and degrade ECM proteins such as collagens by changes in the activity of matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). Endo180 is an extracellular fibronectin type II domain involved in lysosomal degradation of collagen which has been shown to mitigate renal fibrosis. More recently, hydrogen sulfide (H2S) has also been shown to mitigate hypertensive renal remodeling, however, its mechanism remains unclear. In this study, our aim was to investigate whether Angiotensin-II (Ang II) treatment alters the expression of Endo180, MMPs and TIMPs leading to dysregulation of collagen metabolism and whether GYY4137 (H2S donor) restores their levels to achieve homeostasis. Mesangial and mouse glomerular endothelial cells (MCs and MGECs respectively) were treated without or with Ang II (200 nM) and GYY4137 (250 μM) for 48hrs. Cell lysates were analyzed for MMP-13, -14, TIMP-1, Endo180, and collagen IV by Western blot, RT-PCR, and immunohistochemistry. In MGECs, Ang II treatment compared to its control decreased MMP-13/TIMP-1 ratio (0.75±0.44 vs. 2.48 ±0.73), and upregulated MMP-14/TIMP-1 ratio (0.64±2.10 vs. 0.96±1.47), and collagen IV (0.77±0.07 vs. 0.58±0.06). GYY4137 treatment mitigated these changes. In contrast, Ang II treatment in MCs decreased Endo180 compared to control (0.72±0.04 vs. 1.07±0.23), but did not alter the expression of MMP-13/TIMP-1, MMP-14/TIMP-1 ratios, and collagen IV level compared to control or MGECs. Similarly, immunostaining showed downregulation of MMP-13 and Endo180 in Ang II treated MGECs which was normalized following GYY4137 treatment. Endo180 was also normalized in MCs following GYY4137 treatment however, there was no change in MMP-14/TIMP-1 ratio or collagen IV level. We conclude that Ang II treatment causes adverse ECM remodeling in MGECs via downregulation of Endo180 and MMP-13 and upregulation of MMP-14 and TIMP-1 and in MCs by decreasing Endo180, and GYY4137 mitigates these changes in part, by modulating Endo180/MMP/TIMP pathway.

scholarly journals Exosomics

2020 ◽  
Vol 26 ◽  
Author(s):  
Thanasis Mitsis ◽  
Katerina Pierouli ◽  
Kalliopi Io Diakou ◽  
Eleni Papakonstantinou ◽  
Flora Bacopoulou ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Biomedical Applications ◽  
Drug Carriers ◽  
Biological Pathways ◽  
Biological Processes ◽  
The Past ◽  
Current Trends ◽  
Pathological Conditions ◽  
Concise Information ◽  
Non Coding Rnas

Extracellular vesicles have been the focus of a large number of studies in the past five years. Exosomes, a subgroup of extracellular vesicles, are of particularly high interest because they partake in a wide number of biological pathways.  Produced by a variety of cells, exosomes have an important role in both physiological and pathological conditions.  Exosome cargo heavily defines the vesicles' unique characteristics, and cargo with the most intriguing prospects in its' biomedical applications is the non-coding RNAs.  Non-coding RNAs, and specifically microRNAs are implicated in the regulation of many biological processes and have been associated with numerous diseases. Exosomes containing such important cargo can be used as biomarkers, therapeutic biomaterials, or even drug carriers. The potential media use of exosomes seems promising. However, some obstacles should be overcome before their clinical application.  Synthetic exosome-like biomolecules may be a solution, but their production is still in their beginning stages. This review provides concise information regarding the current trends in exosome studies.

scholarly journals An In Vitro Study on Extracellular Vesicles From Adipose-Derived Mesenchymal Stem Cells in Protecting Stress Urinary Incontinence Through MicroRNA-93/F3 Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Lu Wang ◽  
Yali Wang ◽  
Yuancui Xiang ◽  
Jinping Ma ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Urinary Incontinence ◽  
Stress Urinary Incontinence ◽  
Extracellular Vesicles ◽  
Satellite Cells ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Collagen Iii ◽  
Primary Fibroblasts

Since the potential roles of extracellular vesicles secreted by adipose-derived mesenchymal stem cells (ADSCs) are not well understood in collagen metabolism, the purpose of this research was to evaluate the effects of ADSCs-extracellular vesicles in stress urinary incontinence and the regulatory mechanism of delivered microRNA-93 (miR-93). ADSCs were isolated and cultured, and ADSCs-extracellular vesicles were extracted and identified. Stress urinary incontinence primary fibroblasts or satellite cells were treated with ADSCs-extracellular vesicles to detect the expression of Elastin, Collagen I, and Collagen III in fibroblasts and Pax7 and MyoD in satellite cells. After transfecting ADSCs with miR-93 mimics or inhibitors, extracellular vesicles were isolated and treated with stress urinary incontinence primary fibroblasts or satellite cells to observe cell function changes. The online prediction and luciferase activity assay confirmed the targeting relationship between miR-93 and coagulation factor III (F3). The rescue experiment verified the role of ADSCs-extracellular vesicles carrying miR-93 in stress urinary incontinence primary fibroblasts and satellite cells by targeting F3. ADSCs-extracellular vesicles treatment upregulated expression of Elastin, Collagen I, and Collagen III in stress urinary incontinence primary fibroblasts and expression of Pax7 and MyoD in stress urinary incontinence primary satellite cells. miR-93 expression was increased in stress urinary incontinence primary fibroblasts or satellite cells treated with ADSCs-extracellular vesicles. Extracellular vesicles secreted by ADSCs could deliver miR-93 to fibroblasts and then negatively regulate F3 expression; ADSCs-extracellular vesicles could reverse the effect of F3 on extracellular matrix remodeling in stress urinary incontinence fibroblasts. miR-93 expression was also increased in stress urinary incontinence primary satellite cells treated by ADSCs-extracellular vesicles. Extracellular vesicles secreted by ADSCs were delivered to satellite cells through miR-93, which directly targets F3 expression and upregulates Pax7 and MyoD expression in satellite cells. Our study indicates that miR-93 delivered by ADSCs-extracellular vesicles could regulate extracellular matrix remodeling of stress urinary incontinence fibroblasts and promote activation of stress urinary incontinence satellite cells through targeting F3.

scholarly journals Antigen-presenting cell-derived extracellular vesicles in accelerating atherosclerosis

2021 ◽  
Vol 8 (3) ◽  
pp. 4258-4265
Author(s):  
Alexander E Berezin ◽  
Alexander A Berezin
Keyword(s):  
Extracellular Vesicles ◽  
T Regulatory Cells ◽  
Bioactive Molecules ◽  
Atherosclerotic Plaques ◽  
Macrophage Phenotype ◽  
Non Coding Rnas ◽  
Microvascular Inflammation ◽  
Antigen Presenting ◽  
Endosomal System

Extracellular vesicles (EVs) are a population of heterogeneous particles that originate from the endosomal system or plasma membrane. Antigen-presenting cells (APCs) produce and release a broad spectrum of EVs involved in the pathogenesis of atherosclerosis. APC-derived EVs contain several bioactive molecules, such as non-coding RNAs, cytokines, chemokines, active proteins, immunomodulatory factors, and growth factors. The review focuses on the role of APC-derived EVs in regulating the transformation of macrophage phenotype, shaping foam cells, driving autophagy and/or inhibiting apoptosis of Th4+ cells, T regulatory cells, endothelial and smooth muscle cells (SMCs), as well as in facilitating oxidative stress in vasculature. APC-derived EVs act as triggers of angiogenesis, neovascularization and inflammation through their participation in microvascular inflammation, angiogenesis, development of atherosclerotic plaques, and modulation of their instability.

scholarly journals Macrophage-derived extracellular vesicles: diverse mediators of pathology and therapeutics in multiple diseases

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Yizhuo Wang ◽  
Meng Zhao ◽  
Shuyun Liu ◽  
Jun Guo ◽  
Yanrong Lu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Biological Function ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Bioactive Molecules ◽  
Live Cells ◽  
Therapeutic Effects ◽  
Innate Immune Cells ◽  
Beneficial Effects

Abstract Macrophages (Mφ) are primary innate immune cells that exhibit diverse functions in response to different pathogens or stimuli, and they are extensively involved in the pathology of various diseases. Extracellular vesicles (EVs) are small vesicles released by live cells. As vital messengers, macrophage-derived EVs (Mφ-EVs) can transfer multiple types of bioactive molecules from macrophages to recipient cells, modulating the biological function of recipient cells. In recent years, Mφ-EVs have emerged as vital mediators not only in the pathology of multiple diseases such as inflammatory diseases, fibrosis and cancers, but also as mediators of beneficial effects in immunoregulation, cancer therapy, infectious defense, and tissue repair. Although many investigations have been performed to explore the diverse functions of Mφ-EVs in disease pathology and intervention, few studies have comprehensively summarized their detailed biological roles as currently understood. In this review, we briefly introduced an overview of macrophage and EV biology, and primarily focusing on current findings and future perspectives with respect to the pathological and therapeutic effects of Mφ-EVs in various diseases.

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